Melatonin, represented by the structure below ##STR1## is named systematically as N-[2-(5-methoxy-3-indolyl)ethyl]acetamide. Trivial names for the compound include N-acetyl-5-methoxytryptamine and N-acetyl-O-methylserotonin. Melatonin, a pineal gland hormone, has ovulation inhibitory activity. Chu, Wortman and Axelrod, Endocrinology, 75, 238 (1964) inhibited both the estrous phase of the estrous cycle and ovulation in rats and mice with melatonin--see also Ying and Greep, Endocrinology, 92, 333 (1973).
Several substituted melatonins have been prepared Flaugh et al, J. Med. Chem., 22, 63 (1979) prepared 6-chloro and 6-fluoromelatonin. These compounds showed increased ovulation blocking activity .alpha.-Methyl-6-chloromelatonin was also prepared, but .alpha.-methyl substitution was found to have no increased ovulation-blocking activity when compared to melatonin itself.
Frohn et al. Life Sci. 27, 2043 (1980) prepared N-acetyl 5,6-dimethoxytryptamine and longer alkyl chain N-acyl derivatives. Frohn et al. discuss structure-activity relationships of melatonin analogs, and conclude that only exchange of acetyl for propionyl or butyryl and halogenation at the 6-position are beneficial. All other changes are said to decrease activity. .alpha.-Methyl-6-chloromelatonin was stated to be inactive.
Beta-alkylmelatonins are not described in the prior art. In view of Frohn's teaching that .alpha.-methylation destroys activity .beta.-alkylation would not be expected to produce active ovulation inhibitors. An object of this invention is to provide a group of .beta.-alkyl melatonins having good ovulation inhibition activity.